tbuckley/cabot-search huggingface dataset:
Impaired Awareness of Hypoglycemia in Type 1 Diabetes: A Report of An NIDDK Workshop in October 2021
Authors: Elizabeth R. Seaquist, Karen Teff, Simon R. Heller
Journal: Diabetes Care (2022)

Hypoglycemia remains a limiting factor in the optimal treatment of type 1 diabetes. Repeated episodes of hypoglycemia result in impaired awareness of subsequent hypoglycemic events, inducing a vicious feed-forward cycle and increasing the risk of morbidity and mortality. Why this occurs and how to manage the problem in clinical practice remain uncertain. To address the obstacles and barriers that have hindered progress in this clinically important area, the National Institute of Diabetes and Digestive and Kidney Diseases convened a workshop on 14-15 October 2021. This perspective offers a summary of this outstanding meeting, which brought clinical and basic scientists from the fields of diabetes, neuroscience, psychology, psychiatry, and imaging together, on how to best advance the field of impaired awareness of hypoglycemia and hypoglycemia in general in patients with diabetes.
The heightened importance of the microbiome in cancer immunotherapy
Authors: Clélia Villemin, Anne Six, B. Anne Neville, Trevor D. Lawley, Matthew J. Robinson, Ghaith Bakdash
Journal: Trends in Immunology (2022)

The human microbiome is recognized as a key factor in health and disease. This has been further corroborated by identifying changes in microbiome composition and function as a novel hallmark in cancer. These effects are exerted through microbiome interactions with host cells, impacting a wide variety of developmental and physiological processes. In this review, we discuss some of the latest findings on how the bacterial component of the microbiome can influence outcomes for different cancer immunotherapy modalities, highlighting identified mechanisms of action. We also address the clinical efforts to utilize this knowledge to achieve better responses to immunotherapy. A refined understanding of microbiome variations in patients and microbiome–host interactions with cancer therapies is essential to realize optimal clinical responses.
Activation of the PP2A-B56α heterocomplex synergizes with venetoclax therapies in AML through BCL2 and MCL1 modulation
Authors: Irene Peris, Silvia Romero-Murillo, Elena Martínez-Balsalobre, Caroline C. Farrington, Elena Arriazu, Nerea Marcotegui, Marta Jiménez-Muñoz, Cristina Alburquerque-Prieto, Andrea Torres-López, Vicente Fresquet, Jose A. Martínez-Climent, Maria C. Mateos, Maria L. Cayuela, Goutham Narla, Maria D. Odero, Carmen Vicente
Journal: Blood (2022)
Reply to A. Mangla and E. Hindié
Authors: Marc D. Moncrieff, Vernon K. Sondak, John F. Thompson, Jonathan S. Zager
Journal: Journal of Clinical Oncology (2022)

We read with interest the correspondence from Dr Mangla 1 and Dr Hindi é2 concerning our recent study, 3 which stratified patients with American Joint Committee on Cancer (AJCC)-8th edition stage IIIA melanoma into lowrisk and high-risk subgroups on the basis of the sentinel node (SN) maximum tumor deposit size (MTDS).We found that MTDS $ 0.3 mm represented high-risk micrometastatic disease, whereas outcomes for patients with MTDS below that threshold were like those of SN biopsy (SNB)-negative patients.The primary end point was disease-specific survival (DSS), but the 0.3 mm MTDS cutpoint also reflected distant metastasis-free survival.
DDX41-associated susceptibility to myeloid neoplasms
Authors: Hideki Makishima, Teresa V. Bowman, Lucy A. Godley
Journal: Blood (2022)

Deleterious germ line DDX41 variants confer risk for myeloid neoplasms (MNs) and less frequently for lymphoid malignancies, with autosomal dominant inheritance and an estimated prevalence of 3% among MNs. Germ line DDX41 variants include truncating alleles that comprise about two-thirds of all alleles, missense variants located preferentially within the DEAD-box domain, and deletion variants. The identification of a truncating allele on tumor-based molecular profiling should prompt germ line genetic testing because >95% of such alleles are germ line. Somatic mutation of the wild-type DDX41 allele occurs in about half of MNs with germ line DDX41 alleles, typically in exons encoding the helicase domain and most frequently as R525H. Several aspects of deleterious germ line DDX41 alleles are noteworthy: (1) certain variants are common in particular populations, (2) MNs develop at older ages typical of de novo disease, challenging the paradigm that inherited cancer risk always causes disease in young people, (3) despite equal frequencies of these variants in men and women, men progress to MNs more frequently, suggesting a gender-specific effect on myeloid leukemogenesis, and (4) individuals with deleterious germ line DDX41 variants develop acute severe graft-versus-host disease after allogeneic hematopoietic cell transplantation with wild-type donors more than others unless they receive posttransplant cyclophosphamide, suggesting a proinflammatory milieu that stimulates donor-derived T cells. Biochemical studies and animal models have identified DDX41's ability to interact with double-stranded DNA and RNA:DNA hybrids with roles in messenger RNA splicing, ribosomal RNAs or small nucleolar RNAs processing, and modulation of innate immunity, disruption of which could promote inflammation and drive tumorigenesis.
Financial Burden in Blood or Marrow Transplantation Survivors During the COVID-19 Pandemic: A BMTSS Report
Authors: Smita Bhatia, Chen Dai, Lindsey Hageman, Jessica Wu, Elizabeth Schlichting, Arianna Siler, Erin Funk, Jessica Hicks, Shawn Lim, Nora Balas, Alysia Bosworth, Hok Sreng Te, Liton Francisco, Ravi Bhatia, Stephen J. Forman, F. Lennie Wong, Mukta Arora, Saro H. Armenian, Daniel J. Weisdorf, Wendy Landier
Journal: Journal of Clinical Oncology (2022)

The financial burden experienced by blood or marrow transplant (BMT) survivors during the COVID-19 pandemic remains unstudied. We evaluated the risk for high out-of-pocket medical costs and associated financial burden experienced by BMT survivors and a sibling comparison group during the COVID-19 pandemic.
Assessing Pretomanid for Tuberculosis (APT), a Randomized Phase 2 Trial of Pretomanid-Containing Regimens for Drug-Sensitive Tuberculosis: 12-Week Results
Authors: Kelly E. Dooley, Bronwyn Hendricks, Nikhil Gupte, Grace Barnes, Kim Narunsky, Colleen Whitelaw, Tanya Smit, Elisa H. Ignatius, Adine Friedman, Susan E. Dorman, Rodney Dawson
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Pretomanid is a new nitroimidazole with proven treatment-shortening efficacy in drug-resistant tuberculosis. Pretomanid-rifamycin-pyrazinamide combinations are potent in mice but have not been tested clinically. Rifampicin, but not rifabutin, reduces pretomanid exposures.
Reassessing the Benefits and Harms of Risk-Reducing Medication Considering the Persistent Risk of Breast Cancer Mortality in Estrogen Receptor–Positive Breast Cancer
Authors: Jinani Jayasekera, Amy Zhao, Clyde Schechter, Kathryn Lowry, Jennifer M. Yeh, Marc D. Schwartz, Suzanne O'Neill, Karen J. Wernli, Natasha Stout, Jeanne Mandelblatt, Allison W. Kurian, Claudine Isaacs
Journal: Journal of Clinical Oncology (2022)

Recent studies, including a meta-analysis of 88 trials, have shown higher than expected rates of recurrence and death in hormone receptor-positive breast cancer. These new findings suggest a need to re-evaluate the use of risk-reducing medication to avoid invasive breast cancer and breast cancer death in high-risk women.We adapted an established Cancer Intervention and Surveillance Modeling Network model to evaluate the lifetime benefits and harms of risk-reducing medication in women with a ≥ 3% 5-year risk of developing breast cancer according to the Breast Cancer Surveillance Consortium risk calculator. Model input parameters were derived from meta-analyses, clinical trials, and large observational data. We evaluated the effects of 5 years of risk-reducing medication (tamoxifen/aromatase inhibitors) with annual screening mammography ± magnetic resonance imaging (MRI) compared with no screening, MRI, or risk-reducing medication. The modeled outcomes included invasive breast cancer, breast cancer death, side effects, false positives, and overdiagnosis. We conducted subgroup analyses for individual risk factors such as age, family history, and prior biopsy.Risk-reducing tamoxifen with annual screening (± MRI) decreased the risk of invasive breast cancer by 40% and breast cancer death by 57%, compared with no tamoxifen or screening. This is equivalent to an absolute reduction of 95 invasive breast cancers, and 42 breast cancer deaths per 1,000 high-risk women. However, these drugs are associated with side effects. For example, tamoxifen could increase the number of endometrial cancers up to 11 per 1,000 high-risk women. Benefits and harms varied by individual characteristics.The addition of risk-reducing medication to screening could further decrease the risk of breast cancer death. Clinical guidelines for high-risk women should consider integrating shared decision making for risk-reducing medication and screening on the basis of individual risk factors.
Color Atlas of AIDS and HIV Disease
Authors: Charles F. Farthing, Simon E. Brown, Richard C.D. Staughton
Journal: Annals of Internal Medicine (1989)

Part 1 The AIDS epidemic: epidemiology immunology virology the definition of AIDS the antibody response to HIV the HIV antibody test the origin of HIV the clinical spectrum and classification of HIV disease. Part 2 Clinical manifestation of HIV disease: HIV seroconversion illness, or acute HIV  lymphadenopathy weight loss oral cavity disease skin disease ENT problems Kaposi's sarcoma pulmonary disease diseases of the nervous system gastrointestinal disease lymphoma paediatric HIV disease. Part 3: Other sexually transmitted diseases in HIV positive patients. Part 4: Counselling of patients with HIV disease. Part 5: Tranmsmission and prevention of HIV disease. Appendices: 1 - the full definition of AIDS 2 - AIDS in Africa, M.Rolfe.
Cerebrospinal fluid methylome-based liquid biopsies for accurate malignant brain neoplasm classification
Authors: Jeffrey A Zuccato, Vikas Patil, Sheila Mansouri, Mathew Voisin, Ankur Chakravarthy, Shu Yi Shen, Farshad Nassiri, Nicholas Mikolajewicz, Mara Trifoi, Anna Skakodub, Brad Zacharia, Michael Glantz, Daniel D De Carvalho, Alireza Mansouri, Gelareh Zadeh
Journal: Neuro-Oncology (2022)

Abstract Background Resolving the differential diagnosis between brain metastases (BM), glioblastomas (GBM), and central nervous system lymphomas (CNSL) is an important dilemma for the clinical management of the main three intra-axial brain tumor types. Currently, treatment decisions require invasive diagnostic surgical biopsies that carry risks and morbidity. This study aimed to utilize methylomes from cerebrospinal fluid (CSF), a biofluid proximal to brain tumors, for reliable non-invasive classification that addresses limitations associated with low target abundance in existing approaches. Methods Binomial GLMnet classifiers of tumor type were built, in fifty iterations of 80% discovery sets, using CSF methylomes obtained from 57 BM, GBM, CNSL, and non-neoplastic control patients. Publicly-available tissue methylation profiles (N = 197) on these entities and normal brain parenchyma were used for validation and model optimization. Results Models reliably distinguished between BM (area under receiver operating characteristic curve [AUROC] = 0.93, 95% confidence interval [CI]: 0.71–1.0), GBM (AUROC = 0.83, 95% CI: 0.63–1.0), and CNSL (AUROC = 0.91, 95% CI: 0.66–1.0) in independent 20% validation sets. For validation, CSF-based methylome signatures reliably distinguished between tumor types within external tissue samples and tumors from non-neoplastic controls in CSF and tissue. CSF methylome signals were observed to align closely with tissue signatures for each entity. An additional set of optimized CSF-based models, built using tumor-specific features present in tissue data, showed enhanced classification accuracy. Conclusions CSF methylomes are reliable for liquid biopsy-based classification of the major three malignant brain tumor types. We discuss how liquid biopsies may impact brain cancer management in the future by avoiding surgical risks, classifying unbiopsiable tumors, and guiding surgical planning when resection is indicated.
Immunosuppressive Extracellular Vesicles in CLL
Authors: Wenqun Zhong, Wei Guo
Journal: Blood Cancer Discovery (2022)

Cancer cells need to evade the immune system for their progression. In this issue of Blood Cancer Discovery, Gargiulo and colleagues report that in a mouse model of chronic lymphocytic leukemia, small extracellular vesicles inhibit antitumor immunity by altering CD8 T-cell transcriptome, proteome, and metabolome. See related article by Gargiulo et al., p. 54 (9).
Interferon-dependent SLC14A1+ cancer-associated fibroblasts promote cancer stemness via WNT5A in bladder cancer
Authors: Zikun Ma, Xiangdong Li, Yize Mao, Chen Wei, Zhuoli Huang, Guibo Li, Jianhua Yin, Xiaoyu Liang, Zhuowei Liu
Journal: Cancer Cell (2022)
Single low-dose INC280-loaded theranostic nanoparticles achieve multirooted delivery for MET-targeted primary and liver metastatic NSCLC
Authors: Yige Sun, Jie Yang, Yingbo Li, Jing Luo, Jiemei Sun, Daoshuang Li, Yuchen Wang, Kai Wang, Lili Yang, Lina Wu, Xilin Sun
Journal: Molecular Cancer (2022)

Abstract Background Non-small cell lung cancer (NSCLC) patients with primary tumors and liver metastases have substantially reduced survival. Since mesenchymal-epithelial transition factor (MET) plays a significant role in the molecular mechanisms of advanced NSCLC, small molecule MET inhibitor capmatinib (INC280) hold promise for clinically NSCLC treatment. However, the major obstacles of MET-targeted therapy are poor drug solubility and off-tumor effects, even oral high-dosing regimens cannot significantly increase the therapeutic drug concentration in primary and metastatic NSCLC. Methods We developed a multirooted delivery system INC280-PFCE nanoparticles (NPs) by loading INC280 into perfluoro-15-crown-5-ether for improving MET-targeted therapy. Biodistribution and anti-MET/antimetastatic effects of NPs were validated in orthotopic NSCLC and NSCLC liver metastasis models in a single low-dose. The efficacy of INC280-PFCE NPs was also explored in human NSCLC specimens. Results INC280-PFCE NPs exhibited excellent antitumor ability in vitro. In orthotopic NSCLC models, sustained release and prolonged retention behaviors of INC280-PFCE NPs within tumors could be visualized in real-time by 19 F magnetic resonance imaging ( 19 F-MRI), and single pulmonary administration of NPs showed more significant tumor growth inhibition than oral administration of free INC280 at a tenfold higher dose. Furthermore, a single low-dose INC280-PFCE NPs administered intravenously suppressed widespread dissemination of liver metastasis without systemic toxicity. Finally, we verified the clinical translation potential of INC280-PFCE NPs in human NSCLC specimens. Conclusions These results demonstrated high anti-MET/antimetastatic efficacies, real-time MRI visualization and high biocompatibility of NPs after a single low-dose.
The ciliopathy-associated CPLANE proteins direct basal body recruitment of intraflagellar transport machinery
Authors: Michinori Toriyama, Chanjae Lee, S Paige Taylor, Ivan Duran, Daniel H Cohn, Ange-Line Bruel, Jacqueline M Tabler, Kevin Drew, Marcus R Kelly, Sukyoung Kim, Tae Joo Park, Daniela A Braun, Ghislaine Pierquin, Armand Biver, Kerstin Wagner, Anne Malfroot, Inusha Panigrahi, Brunella Franco, Hadeel Adel Al-lami, Yvonne Yeung, Yeon Ja Choi, Yannis Duffourd, Laurence Faivre, Jean-Baptiste Rivière, Jiang Chen, Karen J Liu, Edward M Marcotte, Friedhelm Hildebrandt, Christel Thauvin-Robinet, Deborah Krakow, Peter K Jackson, John B Wallingford
Journal: Nature Genetics (2016)
Facilitating a high-quality dietary pattern induces shared microbial responses linking diet quality, blood pressure, and microbial sterol metabolism in caregiver-child dyads
Authors: Emily B. Hill, Li Chen, Michael T. Bailey, Amrik Singh Khalsa, Ross Maltz, Kelly Kelleher, Colleen K. Spees, Jiangjiang Zhu, Brett R. Loman
Journal: Gut Microbes (2022)

Low-resource individuals are at increased risk of obesity and cardiovascular disease (CVD), partially attributable to poor dietary patterns and dysfunctional microbiota. Dietary patterns in childhood play critical roles in physiological development and are shaped by caregivers, making caregiver-child dyads attractive targets for dietary interventions to reduce metabolic disease risk. Herein, we targeted low-resource caregiver-child dyads for a 10-week, randomized, controlled, multifaceted lifestyle intervention including: nutrition and physical activity education, produce harvesting, cooking demonstrations, nutrition counseling, and kinetic activites; to evaluate its effects on dietary patterns, CVD risk factors, and microbiome composition. Subjects in the lifestyle intervention group improved total diet quality, increased whole grain intake, decreased energy intake, and enhanced fecal elimination of the microbe-derived metabolite lithocholic acid (LCA) in contrast to control subjects. Microbiomes were highly personalized, similar within dyads, and altered by lifestyle intervention. Differential modeling of microbiome composition identified taxa associated with total diet quality, whole grain intake, and LCA elimination including recognized fiber-degrading bacteria such as Subdoligranulum, and bile acid metabolizing organisms like Bifidobacterium. Inclusion of taxa identified in diet and metabolite modeling within blood pressure models improved prediction accuracy of microbiome-blood pressure associations. Importantly, microbiota-blood pressure relationships were shared between dyads, implying shared host-microbiota responses to lifestyle intervention. Overall, these outcomes provide insight into mechanisms by which dietary interventions impact the gut-cardiovascular axis to reduce future CVD risk. Registered at clinicaltrials.gov: NCT05367674
Response to Comment on Park et al. U-Shaped Associations Between Body Weight Changes and Major Cardiovascular Events in Type 2 Diabetes Mellitus: A Longitudinal Follow-up Study of a Nationwide Cohort of Over 1.5 Million. Diabetes Care 2022;45:1239–1246
Authors: Chan Soon Park, Kyung-Do Han, Hyung-Kwan Kim
Journal: Diabetes Care (2022)
Comment on Park et al. U-Shaped Associations Between Body Weight Changes and Major Cardiovascular Events in Type 2 Diabetes Mellitus: A Longitudinal Follow-up Study of a Nationwide Cohort of Over 1.5 Million. Diabetes Care 2022;45:1239–1246
Authors: Zongming Yang, Yanlin Qu, Kun Chen, Jianbing Wang
Journal: Diabetes Care (2022)
Diabetic Ketoacidosis at Onset of Type 1 Diabetes and Long-term HbA1c in 7,961 Children and Young Adults in the Australasian Diabetes Data Network
Authors: Helen F. Clapin, Arul Earnest, Peter G. Colman, Elizabeth A. Davis, Craig Jefferies, Kym Anderson, Melissa Chee, Philip Bergman, Martin de Bock, Kung-Ting Kao, P. Gerry Fegan, D. Jane Holmes-Walker, Stephanie Johnson, Bruce R. King, Meng Tuck Mok, Kruthika Narayan, Alexia S. Peña Vargas, Richard Sinnott, Benjamin J. Wheeler, Anthony Zimmermann, Maria E. Craig, Jenny J. Couper, Geoff Ambler, Sof Andrikopoulos, Helen Barrett, Jenny Batch, Fergus Cameron, Louise Conwell, Andrew Cotterill, Chris Cooper, Kim Donaghue, Jan Fairchild, Spiros Fourlanos, Sarah Glastras, Peter Goss, Leonie Gray, Shane Hamblin, Paul Hofman, Tony Huynh, Steven James, Tim Jones, Antony Lafferty, Michelle Martin, Robert McCrossin, Kris Neville, Mark Pascoe, Ryan Paul, Dorota Pawlak, Liza Phillips, Darrell Price, Christine Rodda, David Simmons, Carmel Smart, Monique Stone, Steve Stranks, Elaine Tham, Glenn Ward, Helen Woodhead
Journal: Diabetes Care (2022)

OBJECTIVE The relationship between diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes and long-term glycemic control varies between studies. We aimed, firstly, to characterize the association of DKA and its severity with long-term HbA1c in a large contemporary cohort, and secondly, to identify other independent determinants of long-term HbA1c. RESEARCH DESIGN AND METHODS Participants were 7,961 children and young adults diagnosed with type 1 diabetes by age 30 years from 2000 to 2019 and followed prospectively in the Australasian Diabetes Data Network (ADDN) until 31 December 2020. Linear mixed-effect models related variables to HbA1c. RESULTS DKA at diagnosis was present in 2,647 participants (33.2%). Over a median 5.6 (interquartile range 3.2, 9.4) years of follow-up, participants with severe, but not moderate or mild, DKA at diagnosis had a higher mean HbA1c (+0.23%, 95% CI 0.11,0.28; [+2.5 mmol/mol, 95% CI 1.4,3.6]; P &amp;lt; 0.001) compared with those without DKA. Use of continuous subcutaneous insulin infusion (CSII) was independently associated with a lower HbA1c (−0.28%, 95% CI −0.31, −0.25; [−3.1 mmol/mol, 95% CI −3.4, −2.8]; P &amp;lt; 0.001) than multiple daily injections, and CSII use interacted with severe DKA to lower predicted HbA1c. Indigenous status was associated with higher HbA1c (+1.37%, 95% CI 1.15, 1.59; [+15.0 mmol/mol, 95% CI 12.6, 17.4]; P &amp;lt; 0.001), as was residing in postcodes of lower socioeconomic status (most vs. least disadvantaged quintile +0.43%, 95% CI 0.34, 0.52; [+4.7 mmol/mol, 95% CI 3.4, 5.6]; P &amp;lt; 0.001). CONCLUSIONS Severe, but not mild or moderate, DKA at diagnosis was associated with a marginally higher HbA1c over time, an effect that was modified by use of CSII. Indigenous status and lower socioeconomic status were independently associated with higher long-term HbA1c.
Hemispherically lateralized rhythmic oscillations in the cingulate-amygdala circuit drive affective empathy in mice
Authors: Seong-Wook Kim, Minsoo Kim, Jinhee Baek, Charles-Francois Latchoumane, Gireesh Gangadharan, Yongwoo Yoon, Duk-Soo Kim, Jin Hyung Lee, Hee-Sup Shin
Journal: Neuron (2022)
Widespread, human-associated redondoviruses infect the commensal protozoan Entamoeba gingivalis
Authors: Emma L. Keeler, Carter Merenstein, Shantan Reddy, Louis J. Taylor, Ana G. Cobián-Güemes, Urvi Zankharia, Ronald G. Collman, Frederic D. Bushman
Journal: Cell Host & Microbe (2022)